APPLICANT'S ABSTRACT: Proposed is a 12-week, randomized, double-blind, placebo controlled trial of sertraline in methadone maintenance patients who have a current depressive disorder determined by lifetime psychiatric history and who are currently using illicit drugs. Responders during the first 12 weeks are followed under the blind for an additional 12 weeks. Depression is prevalent in methadone patients and is associated with poor outcome. Studies of tricyclic antidepressants in depressed methadone patients, including a recently completed randomized controlled trial of imipramine by our group, suggest robust antidepressant effects but relatively modest impact upon illicit drug use. Sertraline is a specific serotonin re-uptake inhibitor (SSRI), FDA approved for the treatment of depression. Sertraline may have several advantages in depressed methadone patients, including fewer side effects and greater margin of safety. The proposed study is a replication and extension of the prior work with tricyclics, seeking to evaluate and add a new agent to the therapeutic armamentarium available for treatment of depressed methadone patients. The following principal questions will be addressed: 1) Is sertraline effective for treatment of depression in methadone patients compared to placebo? 2) Is sertraline effective in reducing illicit drug use in depressed methadone patients? 3) Is sertraline response maintained during a 12-week double-blind follow-up subsequent to the acute 12-week trial?